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LSUHSC's Nichols to use LSD and fruit flies to identify genes for psychosis/schizo

New Orleans, LA Charles Nichols, PhD, Assistant Professor of Pharmacology at LSU Health Sciences Center New Orleans, has been awarded a grant in the amount of $1.4 million over four years by the National Institutes of Health's National Institute of Mental Health to find and characterize novel genes involved in psychosis and schizophrenia, using novel research methods.

Dr. Nichols' approach is innovative, combining discovery studies with functional and behavioral studies in two different models to determine how mental disorders like psychosis and schizophrenia develop. By studying both a new rodent model of psychosis that he is co-developing, which involves treating rats with the powerful hallucinogenic drug lysergic acid diethylamid (LSD), and the fruit fly, Drosophila melanogaster, analysis of gene function relative to whole animal behavior can be accomplished more rapidly than with traditional rodent models alone.

"We believe that changes in gene function, influenced by abnormal activity in specific regions of the brain regulated by the neurotransmitter serotonin, contribute to neuropsychiatric disorders. The effects of LSD can be very similar to aspects of psychosis in people, but no one really understands how LSD works other than it changes how serotonin functions in the brain," notes Dr. Nichols.

In preliminary studies, Dr. Nichols has shown that, remarkably, both serotonin and hallucinogenic drugs like LSD influence many complex behaviors in the fly directly relevant to those that are abnormal in humans with psychosis and schizophrenia, including aggression, learning and memory, social interaction, and sensory perception.

The LSUHSC research team will probe specific regions of rat brains that correspond to key cognitive centers of the human brain using advanced genomic and proteomic methods to identify abnormally functioning genes and proteins. Additional studies will translate these results to the fruit fly, where the functional role of both the native and mutant forms of the fly version of these genes and proteins will be examined in behaviors relevant to psychosis. Genes and proteins that are abnormally turned on or off by LSD in the rat brain, and found to participate in causing relevant behaviors in the fruit fly, may represent novel therapeutic targets for neuropsychiatric disorders.

Schizophrenia is a debilitating neuropsychiatric disorder that affects about one out of every 100 Americans, and mental disorders are the leading cause of disability in the U.S. and Canada for ages 15-44. Major mental disorders cost the nation at least $193 billion annually in lost earnings alone, according to a 2008 study funded by the National Institute of Mental Health. The World Health Organization has identified schizophrenia as one of the ten most debilitating diseases affecting human beings. While treatments are improving, there are still people who do not respond or only partially respond.

"Our results may lead to new avenues for therapeutics to treat such devastating diseases as schizophrenia and psychosis," says Dr. Nichols.